We propose a comprehensive program project to investigate the relationship of the development of the lymphoid system and immunodeficiency diseases and cancer of man. This renewal program project will coordinate and focus the efforts of ten interrelated projects working in both clinical and fundamental perspectives. The program will be organized into three major areas of research emphasizing: 1. T cell differentiation in man and mouse: a) T Mu and T Gamma Cells in Primary and Secondary Immunodeficiencies; b) Studies on Differentiation of Human T Cells using Cultured Thymic Epithelium and Culture Supernatants as Inducing Agents; c) Human Lymphocyte Differentiation by Thymic Hormones; d) T-cell Induction and its Modulation by Suspected Immunoregulatory Agents. 2. The effects of T cells and T cell factors on B cell differentiation: a) Analysis of the Cellular Basis of Helper and Suppressor Function in Normal Humans and its Relationship to Patients with Primary and Secondary Immunodeficiency; b) Molecular Basis of Immunoregulatory Activity; c) The Role of T-cell Factors on Differentiation of B Cells. 3. Animal experiments (chicken, mouse, pig) which are closely related to the clinical model of immunodeficiency diseases: a) Cellular Origin of Non-B Lymphocytes Bearing Fc Receptors; b) In Vitro Functional Characterization of B Lymphocyte-Deficient Mice; c) Ontogenic development and differentiation of B-lymphocytes in the gnotobiotic miniswine system.